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Background: Thirty-three synthetic driver genes of T-cell proliferation have recently been identified through genome-scale screening. However, the tumor microenvironment (TME) cell infiltration, prognosis, and response to immunotherapy mediated by multiple T cell proliferation-related genes (TRGs) in patients with head and neck squamous cell carcinoma (HNSC) remain unclear. Methods: This study examined the genetic and transcriptional changes in 771 patients with HNSC by analyzing the TRGs from two independent datasets. Two different subtypes were analyzed to investigate their relationship with immune infiltrating cells in the TME and patient prognosis. The study also developed and validated a risk score to predict overall survival (OS). Furthermore, to enhance the clinical utility of the risk score, an accurate nomogram was constructed by combining the characteristics of this study. Results: The low-risk score observed in this study was associated with high levels of immune checkpoint expression and TME immune activation, indicating a favorable OS outcome. Additionally, various factors related to risk scores were depicted. Conclusion: Through comprehensive analysis of TRGs in HNSC, our study has revealed the characteristics of the TME and prognosis, providing a basis for further investigation into TRGs and the development of more effective immunotherapy and targeted therapy strategies.
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Background: Head and neck squamous cell carcinoma (HNSC) is a dangerous cancer that represents an important threat to human health. Niclosamide is an anti-helminthic drug that has received FDA approval. In drug repurposing screens, niclosamide was found to inhibit proliferative activity for a range of tumor types. Its functional effects in HNSC, however, have yet to be established. Methods: MTT and colony formation assays were used to explore the impact of niclosamide on the proliferation of HNSC cells, while wound healing and Transwell assays were employed to assess migration and invasivity. Flow cytometry and Western immunoblotting were respectively used to assess cellular apoptosis and protein expression patterns. An HNSC xenograft tumor model system was used to evaluate the in vivo antitumor activity of niclosamide, and immunofluorescent staining was employed to assess cleaved Caspase3 and Ki67 expression. The ability of niclosamide to prevent metastatic progression in vivo was assessed with a model of pulmonary metastasis. Results: These analyses revealed the ability of niclosamide to suppress HNSC cell migration, proliferation, and invasivity in vitro while promoting apoptotic death. From a mechanistic perspective, this drug suppressed Stat3 phosphorylation and ß-catenin expression, while increasing cleaved Caspase3 levels in HNSC cells and reducing Bcl-2 levels. Importantly, this drug was able to suppress in vivo tumor growth and pulmonary metastasis formation, with immunofluorescent staining confirming that it reduced Ki67 levels and increased cleaved Caspase3 content. Conclusion: In conclusion, these analyses highlight the ability of niclosamide to inhibit HNSC cell migration and proliferative activity while provoking apoptotic death mediated via p-Stat3 and ß-catenin pathway inactivation. Niclosamide thus holds promise for repurposing as a candidate drug for the more effective clinical management of HNSC.
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Acyl-CoA thioesterase 4 (ACOT4) has been reported to be related to acetyl-CoA carboxylase activity regulation; However, its exact functions in liver lipid and glucose metabolism are still unclear. Here, we discovered explored the regulatory roles of ACOT4 in hepatic lipid and glucose metabolism in vitro. We found that the expression level of ACOT4 was significantly increased in the hepatic of db/db and ob/ob mice as well as obese mice fed a high fat diet. Adenovirus-mediated overexpression of ACOT4 promoted gluconeogenesis and high-glucose/high-insulin-induced lipid accumulation and impaired insulin sensitivity in primary mouse hepatocytes, whereas ACOT4 knockdown notably suppressed gluconeogenesis and decreased the triglycerides accumulation in hepatocytes. Furthermore, ACOT4 knockdown increased insulin-induced phosphorylation of AKT and GSK-3ß in primary mouse hepatocytes. Mechanistically, we found that upregulation of ACOT4 expression inhibited AMP-activated protein kinase (AMPK) activity, and its knockdown had the opposite effect. However, activator A769662 and inhibitor compound C of AMPK suppressed the impact of the change in ACOT4 expression on AMPK activity. Our data indicated that ACOT4 is related to hepatic glucose and lipid metabolism, primarily via the regulation of AMPK activity. In conclusion, ACOT4 is a potential target for the therapy of non-alcoholic fatty liver (NAFLD) and type 2 diabetes.
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide. Its occurrence and progression involve the process from simple hepatic steatosis to metabolic dysfunction associated steatohepatitis (MASH), which could develop into advanced liver fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). Growing evidences support that the pathogenesis and progression of MASLD are closely related to immune system dysfunction. This review aims to summarize the association of MASLD with immune disorders and the prospect of using immunotherapy for MASLD.
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Carcinoma Hepatocelular , Hígado Graso , Neoplasias Hepáticas , Enfermedades Metabólicas , Humanos , Cirrosis HepáticaRESUMEN
OBJECTIVES: Deep neck infections (DNIs) are a common and intractable disease encountered in ENT clinics that impose a significant medical and financial burden on affected individuals and their families. However, insufficient data are currently available for predicting outcomes in cases of DNI. The present study thus sought to develop a novel model capable of predicting treatment outcomes of DNI patients just using indicators at the visit. METHODS: Patients with DNIs treated from 2010 to 2022 were included in the present study. Patient data were retrospectively collected from medical records. Risk factors associated with mortality were identified using logistic regression models. A predictive model was constructed based on odds ratios for factors calculated using a multivariate regression model. RESULTS: In total, 153 patients were enrolled in the present study. Risk factors associated with mortality included age >50 years, residence in a rural area, dyspnea at visit, the involvement of multiple infected sites, serum albumin<34 g/L, renal insufficiency, mediastinitis, pulmonary infection, and septic shock. A multivariate regression model revealed that mediastinitis (OR: 7.308, P < 0.001), serum creatinine>95 µmol/L (OR: 23.363, P < 0.05), and serum albumin<34 g/L (OR: 13.837, P < 0.05) were independent predictors of mortality in deep neck infection patients, with serum creatinine>95 µmol/L being particularly critical to the outcomes. Diabetes was not the predictor of mortality but was associated with long-term hospitalization (P < 0.001). CONCLUSIONS: In summary, the model constructed in the present study was capable of estimating the potential for poor outcomes in DNI patients before the initiation of treatment. These findings may help improve doctor-patient communication, especially for those struggling financially.
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INTRODUCTION: Allergic rhinitis is a form of IgE mediated inflammation of the nasal mucosa in response to specific allergens, resulting in typical symptoms. OBJECTIVES: This study was designed with the primary goal of comparing the clinical efficacy of posterior nasal neurectomy with or without pharyngeal neurectomy for the treatment of moderate-to-severe perennial allergic rhinitis. Secondary study aims included a comparison of the severity of comorbidities, including chronic cough and asthma, between patients in these two surgical treatment groups. METHODS: A total of 52 patients were enrolled in this randomized controlled trial and were assigned to either the control group (posterior nasal neurectomy) or the experimental group (posterior nasal neurectomyâ¯+â¯pharyngeal neurectomy). The visual analog scale and rhinoconjunctivitis quality of life questionnaire were used to compare the differences in patient symptoms between baseline and 6-, 12-, and 24-months post-treatment. In addition, patient cough and asthma symptoms were monitored during follow-up via visual analog scale and asthma control test respectively. RESULTS: No significant differences in preoperative scores were evident between groups (pâ¯>â¯0.05). At 6-months post-treatment, there were significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, and asthma control test scores relative to baseline values in experimental group and control group patients (pâ¯<â¯0.05), and this remained true upon 12- and 24-month follow-up. No significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, or asthma control test scores were observed between the two treatment groups at any postoperative follow-up time point (pâ¯>â¯0.05), while coughing severity was found to be significantly reduced in the experimental group relative to the control group (pâ¯<â¯0.05). CONCLUSION: posterior nasal neurectomy can be safely implemented with or without pharyngeal neurectomy in order to effectively treat allergic rhinitis. Combined posterior nasal neurectomy and pharyngeal neurectomy treatment may offer greater value than posterior nasal neurectomy alone for the treatment of allergic rhinitis patients with chronic cough.
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Desnervación , Rinitis Alérgica , Humanos , Calidad de Vida , Rinitis Alérgica/cirugía , Nariz/cirugíaRESUMEN
PURPOSE: This study was conducted to evaluate outcomes in patients presenting with fungus ball of the maxillary sinus (MSFB) and frontal sinusitis who were treated via middle meatal antrostomy alone. METHODS: This was a randomized, controlled study with a parallel group design. Patients with MSFB and frontal sinusitis were randomly assigned to the maxillary middle meatal antrostomy (MMMA) or control (MMMA + frontal sinusotomy) groups. Patient demographics, complaints, imaging findings were analyzed, and surgical outcomes were evaluated using the Lund-Kennedy endoscopic score (LKES) and the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire. RESULTS: In total, 40 patients were separated into two groups, with similar symptoms including nasal obstruction, mucopurulent rhinorrhea, maxillary or frontal pain, blood stained nasal discharge, nasal cacosmia and orbital pain being observed in both groups. Total LKES and SNOT-22 scores were significantly improved in both groups at 6 months post-treatment, with no significant differences in these scores between groups within a mean 6.8-month follow-up. CONCLUSION: These results suggest that frontal sinusotomy is not required to resolve frontal sinusitis associated with MSFB. As such frontal sinusitis appears to be a reactive process caused by fungal ball obstruction, it regresses spontaneously following fungus ball removal, drainage of the maxillary sinus, and middle meatal antrostomy.
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Seno Frontal , Sinusitis Frontal , Sinusitis Maxilar , Enfermedad Crónica , Endoscopía/métodos , Seno Frontal/diagnóstico por imagen , Seno Frontal/cirugía , Sinusitis Frontal/complicaciones , Sinusitis Frontal/diagnóstico por imagen , Sinusitis Frontal/cirugía , Hongos , Humanos , Seno Maxilar/diagnóstico por imagen , Seno Maxilar/cirugía , Sinusitis Maxilar/etiología , Sinusitis Maxilar/cirugía , Resultado del TratamientoRESUMEN
Abstract Introduction Allergic rhinitis is a form of IgE mediated inflammation of the nasal mucosa in response to specific allergens, resulting in typical symptoms. Objectives This study was designed with the primary goal of comparing the clinical efficacy of posterior nasal neurectomy with or without pharyngeal neurectomy for the treatment of moderate-to-severe perennial allergic rhinitis. Secondary study aims included a comparison of the severity of comorbidities, including chronic cough and asthma, between patients in these two surgical treatment groups. Methods A total of 52 patients were enrolled in this randomized controlled trial and were assigned to either the control group (posterior nasal neurectomy) or the experimental group (posterior nasal neurectomy + pharyngeal neurectomy). The visual analog scale and rhinoconjunctivitis quality of life questionnaire were used to compare the differences in patient symptoms between baseline and 6-, 12-, and 24-months post-treatment. In addition, patient cough and asthma symptoms were monitored during follow-up via visual analog scale and asthma control test respectively. Results No significant differences in preoperative scores were evident between groups (p> 0.05). At 6-months post-treatment, there were significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, and asthma control test scores relative to baseline values in experimental group and control group patients (p< 0.05), and this remained true upon 12- and 24-month follow-up. No significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, or asthma control test scores were observed between the two treatment groups at any postoperative follow-up time point (p> 0.05), while coughing severity was found to be significantly reduced in the experimental group relative to the control group (p< 0.05). Conclusion posterior nasal neurectomy can be safely implemented with or without pharyngeal neurectomy in order to effectively treat allergic rhinitis. Combined posterior nasal neurectomy and pharyngeal neurectomy treatment may offer greater value than posterior nasal neurectomy alone for the treatment of allergic rhinitis patients with chronic cough.
Resumo Introdução A rinite alérgica é uma forma de inflamação da mucosa nasal mediada por IgE em resposta a alérgenos específicos, resulta em sintomas típicos. Objetivos Comparar a eficácia clínica da neurectomia nasal posterior com ou sem neurectomia faríngea para o tratamento da rinite alérgica perene de moderada a grave. Além disso, comparar a gravidade das comorbidades, inclusive tosse crônica e asma, entre os pacientes nesses dois grupos de tratamento cirúrgico. Método Foram incluidos neste ensaio clínico randomizado e designados para o grupo controle (neurectomia nasal posterior) ou para o grupo experimental (neurectomia nasal posterior + neurectomia faríngea) 52 pacientes. A escala visual analógica e o questionário de qualidade de vida na rinoconjuntivite (rhinoconjunctivitis quality of life questionnaire) foram usados para comparar as diferenças nos sintomas dos pacientes entre o período inicial e 6, 12 e 24 meses após o tratamento. Além disso, a tosse e os sintomas de asma dos pacientes foram monitorados durante o acompanhamento por meio da escala visual analógica e do teste de controle da asma (asthma control test ), respectivamente. Resultados Nenhuma diferença significante nos escores pré‐operatórios foi evidenciada entre os grupos (p > 0,05). Aos seis meses pós‐tratamento, houve diferenças significantes nos escores da escala visual analógica, no questionário de qualidade de vida na rinoconjuntivite e no teste de controle de asma em relação aos valores basais dos pacientes no grupo experimental e no grupo controle (p < 0,05), o que permaneceu verdadeiro após 12 e 24 meses de acompanhamento. Não foram observadas diferenças significantes nos escores da escala visual analógica e nem no questionário de qualidade de vida para conjuntivite ou no teste de controle da asma entre os dois grupos de tratamento em qualquer momento do acompanhamento pós‐operatório (p > 0,05), enquanto a gravidade da tosse foi significantemente reduzida no grupo experimental em relação ao grupo controle (p < 0,05). Conclusão A neurectomia nasal posterior pôde ser feita com segurança com ou sem neurectomia faríngea para o tratamento eficaz da rinite alérgica. O tratamento combinado com neurectomia nasal posterior e neurectomia faríngea pode oferecer mais benefício do que a neurectomia nasal posterior isolada para o tratamento de pacientes com rinite alérgica e tosse crônica.
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PURPOSE: To assess how expansion sphincter pharyngoplasty (ESP) impacts blood pressure (BP) and health-related quality of life (HRQOL) in hypertensive patients with obstructive sleep apnea (OSA). METHODS: Patients were separated into two groups based upon whether or not they adhered to antihypertensive drug regimens. Patients underwent 24-h ambulatory BP monitoring before and at 6 months post-ESP, while clinical BP measurements and HRQOL questionnaires (SF-36) were conducted over the course of 24 months post-surgery. RESULTS: We enrolled 62 patients, with 25 and 37 in the medicated and non-medicated groups, respectively. Mean 24-h BP differed significantly, with systolic and diastolic BP (SBP and DBP) decreases of 5.3 mmHg and 2.5 mmHg, respectively (P <0.01). Mean 24-h SBP and DBP decreases in the medicated group were 10.2 mmHg and 4.6 mmHg, respectively (P < 0.001), with significant decreases during the daytime of 8.6 mmHg, 3.0 mmHg, and nighttime of 12.3 mmHg, 7.7 mmHg (P <0.001). In the non-medicated treatment group, 24-h SBP and DBP decreases were 1.9 mmHg and 1.1 mmHg (P < 0.005) with significant decreases in mean nighttime BP values of 3.2 mmHg and 1.9 mmHg (P < 0.001). While pre- and postoperative SF-36 results differed significantly, no differences were observed between the two groups. CONCLUSION: ESP decreases BP and improves HRQOL in OSA patients with hypertension, particularly in combination with antihypertensive drugs.